Method and device for generating image showing concentration distribution of biological substances in biological tissue

ABSTRACT

Generating an image of a molar concentration ratio between a first and second biological substance, an absorption spectrum of the first and second biological substance within a predetermined wavelength range including a first, second, third, and fourth isosbestic point, acquiring first imaging data of the tissue using light extracted from white light using a first filter to collectively selectively extract light in a first wavelength range demarcated by the first and second isosbestic point, light in a second wavelength range demarcated by the second and third isosbestic point, and light in a third wavelength range demarcated by the third and fourth isosbestic point; acquiring second imaging data by taking an image of the tissue using light from the white light using a second optical filter to selectively extract light in the second wavelength range; and generating the distribution image on the basis of the first and second imaging data.

TECHNICAL FIELD

The present invention relates to a method and a device for generating animage showing concentration distribution of biological substances in abiological tissue.

BACKGROUND ART

Recently, an endoscope device having a function of photographingspectroscopic image (spectral endoscope device) has been proposed. Byusing such a spectral endoscope device, it is possible to obtaininformation concerning spectral property (e.g., reflection spectrum) ofa biological tissue such as a mucous membrane of a digestive organ. Itis known that the reflection spectrum of a biological tissue reflectsinformation concerning types or densities of components contained in thevicinity of a surface layer of a biological tissue being a measurementtarget. Specifically, it is known that an absorbance calculated from thereflection spectrum of a biological tissue equals to an absorbanceobtained by linearly superimposing absorbances of a plurality ofsubstances that compose the biological tissue.

It is known that composition and amount of substances in a lesionbiological tissue differ from those in a healthy biological tissue. Itis reported in many of the earlier studies that abnormalities of lesionsrepresented by such as cancer are particularly deeply related to acondition of blood, especially to an overall amount of blood or oxygensaturation. Qualifying and quantifying two focused biological tissues byusing spectroscopic feature values within the visible range that the twofocused biological tissues have is a frequently used method in the fieldof spectrographic analysis. Therefore, it is possible to estimateexistence of some kind of lesions in a biological tissue by comparing aspectral characteristic of blood in a biological tissue that includeslesions with a spectral characteristic of blood in a biological tissuethat does not include lesions.

A spectral image is composed of a series of image information takenusing light of different wavelengths, and more detailed spectralinformation of a biological tissue can be obtained from the spectralimage having higher wavelength resolutions (i.e., larger number ofwavelengths used to acquire image information). Patent Document 1discloses an exemplary configuration of a spectral endoscope devicewhich acquires spectral images in a wavelength range of 400-800 nm at 5nm intervals.

PRIOR ART DOCUMENT Patent Document

(Patent Document 1) Japanese Patent Provisional Publication No.2012-245223A

SUMMARY OF THE INVENTION Problem to be Solved

However, in order to acquire spectral images having high wavelengthresolutions, such as the spectral images disclosed in Patent Document 1,lots of images need to be taken while changing an image pick-upwavelength. Furthermore, a large amount of calculation is necessary toanalyze lots of images and thus it takes time to analyze them. That is,relatively complicated photographing operations and calculations needsto be repeated to obtain effective diagnosis support information.Accordingly, there is a problem that it takes time to obtain theeffective diagnosis support information.

The present invention is made in view of the above situation, and theobject of the present invention is to provide a method and a devicecapable of acquiring image information showing distributions ofbiological substances, such as oxygen saturation distribution, in ashort time.

Means for Solving the Problem

According to an embodiment of the present invention, there is provided amethod for generating a distribution image showing a molar concentrationratio between a first biological substance and a second biologicalsubstance included in a biological tissue of which an absorptionspectrum within a predetermined wavelength range has a first isosbesticpoint, a second isosbestic point, a third isosbestic point and a fourthisosbestic point in ascending order of wavelength, comprising: a step ofacquiring first imaging data G₁ by taking an image of the biologicaltissue using light extracted from white light using a first opticalfilter configured to collectively selectively extract light in a firstwavelength range demarcated by the first isosbestic point and the secondisosbestic point, light in a second wavelength range demarcated by thesecond isosbestic point and the third isosbestic point, and light in athird wavelength range demarcated by the third isosbestic point and thefourth isosbestic point; a step of acquiring second imaging data G₂ bytaking an image of the biological tissue using light extracted from thewhite light using a second optical filter configured to selectivelyextract light in the second wavelength range; and a step of generatingthe distribution image on the basis of the first imaging data G₁, andthe second imaging data G₂.

Also, in the above method, the step of generating the distribution imageon the basis of the first imaging data G₁ and the second imaging data G₂may further comprise: a step of acquiring an absorbance A₁ of thebiological tissue in a transmission wavelength range of the firstoptical filter on the basis of the first imaging data G₁; a step ofacquiring an absorbance A₂ of the biological tissue in a transmissionwavelength range of the second optical filter on the basis of the secondimaging data G₂; and a step of generating the distribution image on thebasis of the absorbance A₁ and the absorbance A₂.

Also, in the above method, the step of acquiring the absorbance A₁ mayinclude a step of calculating the absorbance A₁, using Expression 1 orExpression 2; and

A ₁=−log G ₁  (EXPRESSION 1)

A ₁ =−G ₁  (EXPRESSION 2)

the step of acquiring the absorbance A₂ may include a step forcalculating the absorbance A₂ using Expression 3 or Expression 4.

A ₂=−log G ₁  (EXPRESSION 3)

A ₂ =−G ₂  (EXPRESSION 4)

Also, in the above method, the step of generating the distribution imageon the basis of the absorbance A₁ and the absorbance A₂ may include: astep of calculating an index X using Expression 5; and

X=A ₁−2kA ₂  (EXPRESSION 5)

(where k is a constant)

a step for generating the distribution image on the basis of the indexX.

Also, in the above method, the constant k may be 1.

Also, the above method may further comprise a step of acquiring thirdimaging data R₃ by taking an image of the biological tissue using lightextracted from the white light using a third optical filter configuredto selectively extract light in a fourth wavelength range in which anabsorbance of the biological tissue is sufficiently low compared to anabsorbance in the predetermined wavelength range, and the step ofacquiring the absorbance A₁ may include: a step of calculating a firststandardized reflectivity SR₁ by dividing the first imaging data G₁ bythe third imaging data R₃; and a step of calculating the absorbance A₁using Expression 6 or Expression 7, and

A ₁=−log SR ₁  (EXPRESSION 6)

A ₁ =−SR ₁  (EXPRESSION 7)

the step of acquiring the absorbance A₂ may include: a step ofcalculating a second standardized reflectivity SR₂ by dividing thesecond imaging data G₂ by the third imaging data R₃; and a step ofcalculating the absorbance A₂ using Expression 8 or Expression 9.

A ₂=−log SR ₂  (EXPRESSION 8)

A ₂ =−SR ₂  (EXPRESSION 9)

Also, the above method may further comprise: a step of acquiring a firstbaseline image data BL₁ by taking an image of a colorless colorreference board using light extracted from the white light using thefirst optical filter; and a step of acquiring a second baseline imagedata BL₂ by taking an image of the reference board using light extractedfrom the white light using the second optical filter, and the step ofcalculating the first standardized reflectivity SR₁ may include a stepof dividing the first imaging data G₁ by the first baseline image dataBL₁, and the step of calculating the second standardized reflectivitySR₂ may include a step of dividing the second imaging data G₂ by thesecond baseline image data BL₂.

Also, in the above method, the fourth wavelength range may be 650 nmband, and the third imaging data R₃ may be imaging data taken by alight-receiving element, to which an R filter is provided, included inan image pick-up device provided with an RGB color filter.

Also, in the above method, the constant k may be determined such thatthe index X, acquired on the basis of the first imaging data G₁ and thesecond imaging data G₂ acquired by taking images of a biological tissueof which the molar concentration ratio is known, becomes closest to atheoretical index X.

Also, in the above method, the measured index X for each of a pluralityof biological tissues, each having a known molar concentration ratiothat is different from each other, may be acquired and the constant kmay be determined such that a calibration curve showing a relationshipbetween the known molar concentration ratio and the measured index Xbecomes closest to a reference line showing a relationship between theknown molar concentration ratio and the theoretical index X.

Also, in the above method, the light extracted from the white lightusing the first optical filter in the step of acquiring the firstimaging data G₁ may be dimmed such that an exposure when acquiring thefirst imaging data G₁ and an exposure when acquiring the second imagingdata G₂ become equivalent.

Also, in the above method, the two types of biological substances may beoxyhemoglobin and deoxyhemoglobin, and the molar concentration ratio ofthe first biological substance and the second biological substanceincluded in the biological tissue may be oxygen saturation.

Also, in the above method, the predetermined wavelength range may be a Qband of hemoglobin, and the first imaging data G₁ and the second imagingdata G₂ may be imaging data taken by a light-receiving element, to whicha G filter is provided, included in an image pick-up device providedwith an RGB color filter.

Further, according to an embodiment of the present invention, there isprovided a device for generating a distribution image showing a molarconcentration ratio between a first biological substance and a secondbiological substance included in a biological tissue of which anabsorption spectrum within a predetermined wavelength range has a firstisosbestic point, a second isosbestic point, a third isosbestic pointand a fourth isosbestic point in ascending order of wavelengthcomprising: a light source which emits white light; a first opticalfilter configured to collectively selectively extract light in a firstwavelength range demarcated by the first isosbestic point and the secondisosbestic point, light in a second wavelength range demarcated by thesecond isosbestic point and the third isosbestic point, and light in athird wavelength range demarcated by the third isosbestic point and thefourth isosbestic point from the white light; a second optical filterconfigured to selectively extract light in the second wavelength rangefrom the white light; a switching means configured to switch between thefirst optical filter and the second optical filter; an image pick-updevice configured to take an image of the biological tissue using thelight emitted by the light source; and an image processor unitconfigured to generate the distribution image on the basis of imagingdata generated by the image pick-up device.

Also, the above device may be an endoscope device comprising anendoscope provided at a tip portion.

Effects of the Invention

According to the present invention, image information showingdistributions of biological substances, such as oxygen saturationdistribution, can be acquired in a short time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an absorption spectrum of hemoglobin at Q band.

FIG. 2 is a block chart illustrating an endoscope device according tothe embodiment of the present invention.

FIG. 3 shows transmission spectra of color filters which areaccommodated in an image pick-up device.

FIG. 4 is an external view of a rotating filter.

FIG. 5 is a flowchart explaining an image generating process accordingto the embodiment of the present invention.

FIG. 6 shows exemplary calibration curves used to determine a correctioncoefficient k.

FIG. 7 shows exemplary endoscopic images generated using an endoscopedevice according to the embodiment of the present invention. (a) is anormal observation image, and (b) is an oxygen saturation distributionimage.

EMBODIMENTS FOR CARRYING OUT THE INVENTION

In the following, an embodiment according to the present invention isdescribed with reference to the accompanying drawings.

An endoscope device according to the embodiment of the present inventiondescribed below is a device that quantitatively analyzes biologicalinformation (e.g., oxygen saturation) of an object on the basis of aplurality of images taken using light of different wavelengths anddisplays the analysis result as images. In a quantitative analysis ofthe oxygen saturation described below, a characteristic that a spectralproperty of blood (i.e., spectral property of hemoglobin) continuouslychanges in accordance with the oxygen saturation is used.

(Principles for Calculation of Spectral Property of Hemoglobin andOxygen Saturation)

Before explaining a detailed configuration of an endoscope deviceaccording to the embodiment of the present invention, principles forcalculation of the spectral property of hemoglobin and the oxygensaturation used in the embodiment will be described.

FIG. 1 shows an absorption spectrum of hemoglobin at wavelengths ofaround 550 nm. Hemoglobin has a strong absorption band, derived fromporphyrin, called Q band at wavelengths of around 550 nm. The absorptionspectrum of hemoglobin changes in accordance with the oxygen saturation(ratio of oxyhemoglobin to the overall hemoglobin). A waveform shown ina solid line in FIG. 1 is an absorption spectrum of hemoglobin when theoxygen saturation is 100% (i.e., an absorption spectrum of oxyhemoglobinHbO), and a waveform shown in a long-dashed line is an absorptionspectrum of hemoglobin when the oxygen saturation is 0% (i.e., anabsorption spectrum of deoxyhemoglobin Hb). Waveforms shown inshort-dashed lines are absorption spectra of hemoglobin (a mixture ofoxyhemoglobin and deoxyhemoglobin) at oxygen saturations of between 0%and 100% (10, 20, 30, . . . , 90%).

As shown in FIG. 1, at Q band, oxyhemoglobin and deoxyhemoglobin showpeak wavelengths that differ from each other. Specifically,oxyhemoglobin has an absorption peak P1 at a wavelength of around 542nm, and an absorption peak P3 at a wavelength of around 576 nm. On theother hand, deoxyhemoglobin has an absorption peak P2 at a wavelength ofaround 556 nm. Since FIG. 1 shows a two-component absorption spectrum inwhich a sum of a concentration of each component (oxyhemoglobin anddeoxyhemoglobin) is constant, isosbestic points E1, E2, E3 and E4, whereabsorbances are constant regardless of the concentration of eachcomponent (i.e., oxygen saturation), appear. In the followingdescription, a wavelength range between isosbestic points E1 and E2 isreferred to as wavelength range R1, a wavelength range betweenisosbestic points E2 and E3 is referred to as wavelength range R2, and awavelength range between isosbestic points E3 and E4 is referred to aswavelength range R3. Further, a wavelength range between isosbesticpoints E1 and E4 is referred to as wavelength range R0.

As shown in FIG. 1, between neighboring isosbestic points, absorbance ofhemoglobin monotonically increases or decreases with the oxygensaturation. Further, between neighboring isosbestic points, absorbanceof hemoglobin almost linearly changes with the oxygen saturation.

Specifically, absorbances A_(R1) and A_(R3) of hemoglobin at wavelengthranges R1 and R3 linearly increases with oxyhemoglobin concentration(oxygen saturation), and absorbance A_(R), of hemoglobin at wavelengthrange R2 linearly increases with deoxyhemoglobin concentration(1—“oxygen saturation”). Therefore, an index X, defined by the followingExpression 10, linearly increases with oxyhemoglobin concentration(oxygen saturation).

X=(A _(R1) +A _(R3))−A _(R2)  (EXPRESSION 10)

Therefore, the oxygen saturation can be calculated from the index X byexperimentally acquiring a quantitative relationship between the oxygensaturation and the index X.

(Configuration of Endoscope Device)

FIG. 2 is a block chart illustrating an endoscope device 1 according tothe embodiment of the present invention. The endoscope device 1 of thepresent embodiment comprises an electronic endoscope 100, a processor200 and a monitor 300. The electronic endoscope 100 and the monitor 300are detachably connected to the processor 200. Also, the processor 200includes therein a light source unit 400 and an image processor unit500.

The electronic endoscope 100 has an insertion tube 110 to be insertedinto a body cavity. The electronic endoscope 100 is provided with alight guide 131 which extends over the full length of the electronicendoscope 100. One end portion of the light guide 131 (a tip portion 131a) is arranged close to a tip portion of the insertion tube 110 (aninsertion tube tip portion 111), and the other end portion of the lightguide 131 (a proximal end portion 131 b) is connected to the processor200. The processor 200 includes therein the light source unit 400comprising a light source lamp 430, e.g., a Xenon lamp which generates alarge amount of white light WL. The illumination light IL generated bythe light source unit 400 is incident on the end portion 131 b of thelight guide 131. The light which is incident on the proximal end portion131 b of the light guide 131 is guided to the tip portion 131 a throughthe light guide 131, and is emitted from the tip portion 131 a. At theinsertion tube tip portion 111 of the electronic endoscope 100, a lightdistribution lens 132 is arranged to face the tip portion 131 a of thelight guide 131. The illumination light IL emitted from the tip portion131 a of the light guide 131 passes through the light distribution lens132, and illuminates the biological tissue T near the insertion tube tipportion 111.

An objective optical system 121 and an image pick-up device 141 isprovided at the insertion tube tip portion 111. A portion of light whichis reflected or scattered by the surface of the biological tissue T(return light) is incident on the objective optical system 121 andcondensed, and forms an image on a light-receiving surface of the imagepick-up device 141. The image pick-up device 141 of the presentembodiment is a color image photographing CCD (Charge Coupled Device)image sensor comprising a color filter 141 a on a light-receivingsurface thereof, but other types of image pick-up device such as CMOS(Complementary Metal Oxide Semiconductor) image sensor may also be used.The color filter 141 a is a so-called on-chip filter, in which an Rfilter that transmits red light, a G filter that transmits green light,and a B filter that transmits blue light are arranged, which is directlyformed on each light-receiving element of the image pick-up device 141.Each of the R filter, G filter and B filter has a spectral propertyshown in FIG. 3. That is, the R filter of the present embodiment is afilter that transmits light having wavelengths of longer than about 570nm, the G filter is a filter that transmits light having wavelengths ofbetween about 470-620 nm, and the B filter is a filter that transmitslight having wavelengths of shorter than about 530 nm.

The image pick-up device 141 is controlled to drive in synchronizationwith a signal processing circuit 550 which will be described later, andperiodically (e.g., at 1/30 seconds interval) outputs imaging signalscorresponding to an image formed on the light-receiving surface. Theimaging signals which are outputted from the image pick-up device 141are sent to the image processor unit 500 of the processor 200 via acable 142.

The image processor unit 500 comprises an A/D conversion circuit 510, atemporary memory 520, a controller 530, a video memory 540 and a signalprocessing circuit 550. The A/D conversion circuit 510 executes A/Dconversion to the image signals transmitted from the image pick-updevice 141 of the electronic endoscope 100 via the cable 142 to outputdigital image data. The digital image data outputted from the A/Dconversion circuit 510 is transmitted to and stored in the temporarymemory 520. The digital image data (imaging signals) includes R digitalimage data (R imaging signal) which is imaged by the light-receivingelement to which the R filter is provided, G digital image data (Gimaging signal) which is taken by the light-receiving element to whichthe G filter is provided, and B digital image data (B imaging signal)which is taken by the light-receiving element to which the B filter isprovided.

The controller 530 processes a piece of or a plurality of pieces ofimage data stored in the temporary memory 520 to generate one piece ofdisplay image data, and transmits the display image data to the videomemory 540. For example, the controller 530 generates display image datasuch as display image data generated from a piece of digital image data,display image data in which a plurality of pieces of image data arearranged, or display image data in which healthy regions and lesionregions are identified or a graph of a reflection spectrum of thebiological tissue T corresponding to a specific pixel (x, y) isdisplayed by generating a reflection spectrum of the biological tissue Tfor each pixel (x, y) on the basis of a plurality of pieces of digitalimage data, and stores them in the video memory 540. The signalprocessing circuit 550 generates video signals having a predeterminedformat (e.g., a format which conforms to NTSC or DVI standard) on thebasis of the display image data stored in the video memory 540, andoutputs the video signals. The video signals outputted from the signalprocessing circuit 550 is inputted to the monitor 300. As a result,endoscopic images taken by the electronic endoscope 100 and the like aredisplayed on the monitor 300.

As described above, the processor 200 has both a function as a videoprocessor for processing the image signals outputted from the imagepick-up device 141 of the electronic endoscope 100, and a function as alight source device for supplying illumination light IL to the lightguide 131 of the electronic endoscope 100 to illuminate the biologicaltissue T being an object.

Other than the above-mentioned light source 430, the light source unit400 comprises a collimator lens 440, a rotating filter 410, a filtercontrol unit 420 and a condenser lens 450. The white light WL emittedfrom the light source 430 is converted by the collimator lens 440 into acollimated beam, transmits through the rotating filter 410, and then isincident on the end portion 131 b of the light guide 131 by thecondenser lens 450.

The rotating filter 410 is a circular plate type optical unit comprisinga plurality of optical filters, and is configured such that atransmission wavelength range thereof changes in accordance with therotation angle thereof. The rotation angle of the rotating filter 410 iscontrolled by the filter control unit 420 connected to the controller530. The spectrum of the illumination light supplied to the light guide131 through the rotating filter 410 can be switched by the controller530 controlling the rotation angle of the rotating filter 410 via thefilter control unit 420.

FIG. 4 is an external view (front view) of the rotating filter 410. Therotating filter 410 comprises a substantially circular plate shapedframe 411, and four fan-shaped optical filters 415, 416, 417, and 418.Around the central axis of the frame 411, four fan-shaped windows 414 a,414 b, 414 c, and 414 d are formed at regular intervals, and the opticalfilters 415, 416, 417, and 418 are fit into each of the windows 414 a,414 b, 414 c, and 414 d, respectively. It is noted that, although theoptical filters of the present embodiment are all dielectric multilayerfilm filters, other types of optical filters (e.g., absorbing typeoptical filters or etalon filters in which dielectric multilayers areused as reflecting layers) may also be used.

Also, a boss hole 412 is formed on the central axis of the frame 411. Anoutput axis of a servo motor (not shown) included in the filter controlunit 420 is inserted and fixed to the boss hole 412, and the rotatingfilter 410 rotates along with the output axis of the servo motor.

FIG. 4 shows a state in which the white light WL is incident on theoptical filter 415. However, as the rotating filter 410 rotates in adirection indicated by an arrow, the optical filter on which the whitelight WL is incident changes to 415, 416, 417, 418 in this order, andthus the spectrum of the illumination light IL that transmits therotating filter 410 can be switched.

The optical filters 415 and 416 are optical band-pass filters thatselectively transmit light of 550 nm band. As shown in FIG. 1, theoptical filter 415 is configured to transmit light which is inside thewavelength range between isosbestic points E1 and E4 (i.e., wavelengthrange R0) with low loss, and to cut off light which is outside thewavelength range. Also, the optical filter 416 is configured to transmitlight which is inside the wavelength range between isosbestic points E2and E3 (i.e., wavelength range R2) with low loss, and to cut off lightwhich is outside the wavelength range.

The transmission wavelength ranges of the optical filters 415 and 416(FIG. 1) are included in a transmission wavelength range of the G filterof the color filter 141 a (FIG. 3). Therefore, an image which is formedby light that transmitted through the optical filter 415 or 416 is takenby the light-receiving element to which the G filter is provided, and isacquired as the G digital image data (G imaging signal).

The optical filter 417 is designed to selectively transmit only light of650 nm band (630-650 nm) being a wavelength range in which an absorbanceof hemoglobin in the biological tissue T is low. The transmissionwavelength range of the optical filter 417 is included in a transmissionwavelength range of the R filter of the color filter 141 a (FIG. 3).Therefore, an image which is formed by light that transmitted throughthe optical filter 417 is taken by the light-receiving element to whichthe R filter is provided, and is acquired as the R digital image data (Rimaging signal). The image data acquired by using the illumination lightof 650 nm band is used in a standardization process which will beexplained later.

Also, the optical filter 418 is an ultraviolet cut filter, and theillumination light IL (i.e., a white light) that transmitted through theoptical filter 418 is used for taking normal observation images. It isnoted that the rotating filter 410 may be configured without the opticalfilter 418 to leave the window 414 d of the frame 411 open.

To the window 414 a, a dimmer filter 419 is provided over the opticalfilter 415. The dimmer filter 419 does not have wavelength dependencythroughout the visible light range and thus only decreases a lightamount of the illumination light IL without changing the spectrumthereof. The light amount of the illumination light IL that transmittedthrough the optical filter 415 and the dimmer filter 419 are adjusted toa light amount substantially equivalent to a light amount of theillumination light IL that transmitted through the optical filter 416 byusing the dimmer filter 419. Thus, images can be taken with a properexposure with the same exposure time in both a case where theillumination light IL that passed through the optical filter 415 is usedand a case where the illumination light IL that passed through theoptical filter 416 is used.

In the present embodiment, a metal mesh having a fine mesh size is usedas the dimmer filter 419. Apart from the metal mesh, other types ofdimmer filter such as a half mirror type may be used. Further,transmittances of the optical filters 415 and 416 themselves may beadjusted instead of using the dimmer filter. Further, dimmer filters mayalso be provided to the windows 414 c and 414 d. Further, central anglesof the windows 414 a, 414 b, 414 c, and 414 d (i.e., aperture areas) maybe changed to adjust transmitting light amounts. Further, the exposuretime may be changed for each optical filter instead of using the dimmerfilter.

At the periphery of the frame 411, a through hole 413 is formed. Thethrough hole 413 is formed at a position that is same as a position ofboundary between the windows 414 a and 414 d in the rotating directionof the frame 411. Around the frame 411, a photo interrupter 422 fordetecting the through hole 413 is arranged such that the photointerrupter 422 surrounds a portion of the periphery of the frame 411.The photo interrupter 422 is connected to the filter control unit 420.

The endoscope device 1 of the present embodiment has four operationmodes of a normal observation mode, a spectral analysis (oxygensaturation distribution image displaying) mode, a baseline measuringmode and a calibration mode. The normal observation mode is an operationmode in which a color image is taken using a white light thattransmitted through the optical filter 418. The spectral analysis modeis a mode in which a spectral analysis is carried out on the basis ofthe digital image data taken using illumination light that transmittedthrough the optical filters 415, 416 and 417, and a distribution imageof biomolecules in a biological tissue (e.g., oxygen saturationdistribution image) is displayed. The baseline measuring mode is a modein which an image of a color reference board such as a colorlessdiffusion board (e.g., frosted glass) or reference reflection board istaken as an object using illumination light that passed through theoptical filters 415, 416 and 417, before (or after) executing the actualendoscopic observation, to acquire data to be used in a standardizationprocess which will be described later. The calibration mode is a processin which a spectral analysis is carried out for a sample of whichproperties such as the oxygen saturation is known, and a parameter(correction coefficient k which will be described later) is adjustedsuch that there is no difference between the analysis result and thetheoretical value.

In the normal observation mode, the controller 530 controls the filtercontrol unit 420 to immobilize the rotating filter 410 at a positionwhere the white light WL is incident on the optical filter 418. Then,the digital image data taken by the image pick-up device 141 isconverted to video signals after performing image processes asnecessary, and is displayed on the monitor 300.

In the spectral analysis mode, the controller 530 controls the filtercontrol unit 420 to drive the rotating filter 410 to rotate at constantrotation speed while sequentially taking images of the biological tissueT using illumination light that transmitted through the optical filters415, 416, 417 and 418. Then, an image indicating distribution ofbiomolecules in the biological tissue is generated on the basis ofdigital image data acquired using each of the optical filters 415, 416and 417. Then, a display image in which the distribution image and anormal observation image acquired by using the optical filter 418 arearranged is generated and converted to video signals, and is displayedon the monitor 300.

In the spectral analysis mode, the filter control unit 420 detects arotational phase of the rotating filter 410 on the basis of timing thephoto interrupter 422 detects the through hole 413, compares therotational phase to a phase of a timing signal supplied by thecontroller 530, and adjusts the rotational phase of the rotating filter410. The timing signal from the controller 530 is synchronized with adriving signal for the image pick-up device 141. Therefore, the rotatingfilter 410 is driven to rotate at a substantially constant rotationspeed in synchronization with the driving of the image pick-up device141. Specifically, the rotation of the rotating filter 410 is controlledsuch that the optical filter 415, 416, 417 or 418 (window 414 a, b, c ord) on which the white light WL is to be incident switches each time oneimage (three frames: R, G and B) is taken by the image pick-up device141.

In the baseline measuring mode, the controller 530 controls the filtercontrol unit 420 to rotate the rotating filter 410 while sequentiallytaking images of the color reference board using the illumination lightIL that transmitted through the optical filters 415, 416 and 417. Eachpiece of the G digital image data taken using the illumination light ILthat transmitted through the optical filters 415 and 416 is stored in aninternal memory 531 of the controller 530 as baseline image data BL₄₁₅(x, y) and BL₄₁₆ (x, y), respectively. Further, the R digital image datataken using the illumination light IL that transmitted through theoptical filter 417 is stored in the internal memory 531 of thecontroller 530 as baseline image data BL₄₁₇ (x, y).

Next, an image generation process executed by the image processor unit500 in the spectral analysis mode will be described. FIG. 5 is a flowchart explaining the image generation process.

When the spectral analysis mode is selected by a user's operation, asdescribed above, the filter control unit 420 drives the rotating filter410 to rotate at constant rotation speed. Then, from the light sourceunit 400, the illumination light IL that transmitted through the opticalfilters 415, 416, 417 and 418 are sequentially supplied, and an image issequentially taken using each of the illumination light IL (S1).Specifically, G digital image data G₄₁₅ (x, y) taken using theillumination light IL that transmitted through the optical filter 415, Gdigital image data G₄₁₆ (x, y) taken using the illumination light ILthat transmitted through the optical filter 416, R digital image dataR₄₁₇ (x, y) taken using the illumination light IL that transmittedthrough the optical filter 417, and R digital image data R₄₁₈ (x, y), Gdigital image data G₄₁₈ (x, y) and B digital image data B₄₁₈ (x, y)taken using the illumination light IL that transmitted through theoptical filter (ultraviolet cut filter) 418 are stored in an internalmemory 532 of the controller 530.

Then, the image processor unit 500 executes a pixel selection process S2for selecting pixels to be targets of the following analyzing processes(processes S3-S7) by using the R digital image data R₄₁₈ (x, y), Gdigital image data G₄₁₈ (x, y) and B digital image data B₄₁₈ (x, y)acquired in the process S1. Even if the oxygen saturations or blood flowrates are calculated from color information of pixels corresponding toportions which do not contain blood or portions which colors of tissuesare dominantly influenced by substances other than hemoglobin,meaningful values cannot be obtained and thus the values becomes merenoises. Calculating and providing such noises not only disturbsdiagnosis by the doctor but also causes a bad effect by applying uselessload to the image processor unit 500 to deteriorate processing speed.Therefore, the image generating process of the present embodiment isconfigured to select pixels that are appropriate to the analyzingprocess (i.e., pixels to which the spectral property of hemoglobin isrecorded) and to execute the analyzing process to the selected pixels.

In the pixel selection process S2, only pixels which satisfy all theconditions expressed in Expression 11, Expression 12 and Expression 13are selected as the targets of the analyzing process.

B ₄₁₈(x,y)/G ₄₁₈(x,y)>a ₁  (EXPRESSION 11)

R ₄₁₈(x,y)/G ₄₁₈(x,y)>a ₂  (EXPRESSION 12)

R ₄₁₈(x,y)/B ₄₁₈(x,y)>a ₃  (EXPRESSION 13)

where a₁, a₂ and a₃ are positive constants.

The above three conditional expressions are set on the basis of a valuesize relation, G component<B component<R component, in a transmissionspectrum of blood. It is noted that the pixel selection process S2 maybe executed using one or two of the above three conditional expressions(e.g., using Expression 12 and Expression 13 by focusing on a red colorthat is specific to blood).

Then, the image processor unit 500 executes the standardization process.The standardization process of the present embodiment includes a firststandardization process S3 for correcting properties of the endoscopedevice 1 itself (e.g., transmittances of the optical filters and lightreceiving sensitivities of the image pick-up devices) and a secondstandardization process S4 for correcting reflectivity variations due todifferences in surface states of the biological tissue T being an objectand due to angles of incidence of the illumination light IL to thebiological tissue T.

In the standardization process, the image processor unit 500 calculatesa standardized reflectivity SR₄₁₅ (x, y) using the following Expression14 by using the G digital image data G₄₁₅ (x, y) taken using theillumination light IL that transmitted through the optical filter 415,the R digital image data R₄₁₇ (x, y) taken using the illumination lightIL that transmitted through the optical filter 417, and the baselineimage data BL₄₁₅ (x, y) and BL₄₁₇ (x, y). It is noted that a componentthat is dependent on the properties of the endoscope device 1(instrumental function) is removed by dividing each of the digital imagedata G₄₁₅ (x, y) and R₄₁₇ (x, y) by the respective baseline image dataBL₄₁₅ (x, y) and BL₄₁₇ (first standardization process S3). Also, thereflectivity variations due to differences in surface states of thebiological tissue T and angles of incidence of the illumination light tothe biological tissue T is corrected by dividing the G digital imagedata G₄₁₅ (x, y) by the R digital image data R₄₁₇ (x, y) (secondstandardization process S4).

$\begin{matrix}{{{SR}_{415}\left( {x,y} \right)} = \frac{{G_{415}\left( {x,y} \right)}/{{BL}_{415}\left( {x,y} \right)}}{{R_{417}\left( {x,y} \right)}/{{BL}_{417}\left( {x,y} \right)}}} & \left( {{EXPRESSION}\mspace{14mu} 14} \right)\end{matrix}$

Similarly, a standardized reflectivity SR₄₁₆ (x, y) is calculated usingthe following Expression 15.

$\begin{matrix}{{{SR}_{416}\left( {x,y} \right)} = \frac{{G_{416}\left( {x,y} \right)}/{{BL}_{416}\left( {x,y} \right)}}{{R_{417}\left( {x,y} \right)}/{{BL}_{417}\left( {x,y} \right)}}} & \left( {{EXPRESSION}\mspace{14mu} 15} \right)\end{matrix}$

Absorbances A₄₁₅ (x, y) and A₄₁₅ (x, y) of the biological tissue T withrespect to the illumination light IL that transmitted through theoptical filters 415 and 416 are calculated using the followingExpressions 16 and 17 (S5).

A ₄₁₅(X,y)=−log [SR ₄₁₅(x,y)]  (EXPRESSION 16)

A ₄₁₆(x,y)=−log [SR ₄₁₆(x,y)]  (EXPRESSION 17)

It is noted that the absorbances A₄₁₅ (x, y) and A₄₁₆ (x, y) can beapproximately calculated using the following Expressions 18 and 19.

A ₄₁₅(x,y)=−SR ₄₁₅(x,y)  (EXPRESSION 18)

A ₄₁₆(x,y)=−SR ₄₁₆(x,y)  (EXPRESSION 19)

Furthermore, the spectral analysis can be executed simply by eliminatingthe above mentioned standardization processes (S3, S4). In this case,the absorbances A₄₁₅ (x, y) and A₄₁₆ (x, y) are calculated using thefollowing Expressions 20 and 21.

A ₄₁₅(x,y)=−log G ₄₁₅(x,y)  (EXPRESSION 20)

A ₄₁₆(x,y)=−log G ₄₁₆(x,y)  (EXPRESSION 21)

Also, in this case, the absorbances A₄₁₅ (x, y) and A₄₁₆ (x, y) can beapproximately calculated using the following Expressions 22 and 23,respectively.

A ₄₁₅(x,y)=−G ₄₁₅(x,y)  (EXPRESSION 22)

A ₄₁₆(x,y)=−G ₄₁₆(x,y)  (EXPRESSION 23)

Furthermore, as is obvious from the relationships between the absorptionwavelength ranges R1, R2 and R3 of hemoglobin and the transmissionwavelength ranges of the optical filters 415 and 416 shown in FIG. 1,absorbances A_(R1) (x, y), A_(R2) (x, y) and A_(R3) (x, y) of thebiological tissue T with respect to the wavelength ranges R1, R2 and R3and the absorbances A₄₁₅ (x, y) and A₄₁₆ (x, y) of the biological tissueT with respect to the illumination light IL that transmitted through theoptical filters 415 and 416 have relationships expressed in thefollowing Expressions 24 and 25.

A _(R1)(x,y)+A _(R3)(x,y)=A ₄₁₅(x,y)−kA ₄₁₆(x,y)  (EXPRESSION 24)

A _(R2)(x,y)=kA ₄₁₆(x,y)  (EXPRESSION 25)

Therefore, the index X (Expression 10) is expressed by the followingExpression 26.

                            (EXPRESSION  26) $\begin{matrix}{{X\left( {x,y} \right)} = {\left\lbrack {{A_{R\; 1}\left( {x,y} \right)} + {A_{R\; 3}\left( {x,y} \right)}} \right\rbrack - {A_{R\; 2}\left( {x,y} \right)}}} \\{= {\left\lbrack {{A_{415}\left( {x,y} \right)} - {{kA}_{416}\left( {x,y} \right)}} \right\rbrack - {{kA}_{416}\left( {x,y} \right)}}} \\{= {{A_{415}\left( {x,y} \right)} - {2\; {{kA}_{416}\left( {x,y} \right)}}}}\end{matrix}$

Here, k is a constant (correction coefficient). Since the width of thetransmission wavelength ranges of the optical filters 415 and 416 differsignificantly, the light amounts that transmit through the two filtersalso differ significantly. Therefore, as mentioned above, the dimmerfilter 419 is provided over the optical filter 415, which has a largetransmitting light amount, to control the light amount so that a properexposure can be obtained with the same exposure time even if the opticalfilter is switched. As a result, a quantitative relationship between theabsorbance A₄₁₅ (x, y) acquired using the optical filter 415 and theabsorbance A₄₁₆ (x, y) acquired using the optical filter 416 is broken.Also, the transmittances of the optical filters 415 and 416 within thetransmission wavelength ranges are not 100% and the optical filters 415and 416 have transmission losses that vary depending thereon.Furthermore, there are errors in the transmission wavelength ranges ofthe optical filters 415 and 416. Therefore, even if the dimmer filter419 is not used, the quantitative relationship between the absorbanceA₄₁₅ (x, y) and the absorbance A₄₁₆ (x, y) includes a constant error.The correction coefficient k is a constant for correcting the error ofthe quantitative relationship between the absorbance A₄₁₅ (x, y) and theabsorbance A₄₁₆ (x, y). A method for acquiring the correctioncoefficient k will be described later. It is noted that, in case thiscorrection is not executed, the correction coefficient k is set at 1.

Further, the following Expression 27 can be obtained by arrangingExpression 26 using Expressions 16 and 17.

                                 (EXPRESSION  27) $\begin{matrix}{X = {{- {\log \left\lbrack {{SR}_{415}\left( {x,y} \right)} \right\rbrack}} + {2\; k\; {\log \left\lbrack {{SR}_{416}\left( {x,y} \right)} \right\rbrack}}}} \\{= {{- {\log \left\lbrack \frac{{G_{415}\left( {x,y} \right)}/{{BL}_{415}\left( {x,y} \right)}}{{R_{417}\left( {x,y} \right)}/{{BL}_{417}\left( {x,y} \right)}} \right\rbrack}} + {2\; k\; {\log \left\lbrack \frac{{G_{416}\left( {x,y} \right)}/{{BL}_{416}\left( {x,y} \right)}}{{R_{417}\left( {x,y} \right)}/{{BL}_{417}\left( {x,y} \right)}} \right\rbrack}}}} \\{= {- \left\{ {\left\lbrack {{\log \; {G_{415}\left( {x,y} \right)}} - {\log \; {{BL}_{415}\left( {x,y} \right)}}} \right\rbrack -} \right.}} \\{\left. \left\lbrack {{\log \; {R_{417}\left( {x,y} \right)}} - {\log \; {{BL}_{417}\left( {x,y} \right)}}} \right\rbrack \right\} +} \\{{2\; k\left\{ {\left\lbrack \; {{\log \; {G_{416}\left( {x,y} \right)}} - {\log \; {{BL}_{416}\left( {x,y} \right)}}} \right\rbrack -} \right.}} \\\left. \left\lbrack {{\log \; {R_{417}\left( {x,y} \right)}} - {\log \; {{BL}_{417}\left( {x,y} \right)}}} \right\rbrack \right\} \\{= {{- \left\lbrack {{\log \; {G_{415}\left( {x,y} \right)}} - {\log \; {{BL}_{415}\left( {x,y} \right)}}} \right\rbrack} +}} \\{{{2\; {k\left\lbrack {{\log \; {G_{416}\left( {x,y} \right)}} - {\log \; {{BL}_{416}\left( {x,y} \right)}}} \right\rbrack}} +}} \\{{\left( {1 - {2\; k}} \right)\left\lbrack {{\log \; {R_{417}\left( {x,y} \right)}} - {\log \; {{BL}_{417}\left( {x,y} \right)}}} \right\rbrack}}\end{matrix}$

Therefore, the value of index X can be calculated from the G digitalimage data G₄₁₅ (x, y) and G₄₁₆ (x, y), R digital image data R₄₁₇ (x,y), and the baseline image data BL₄₁₅ (x, y), BL₄₁₆ (x, y) and BL₄₁₇ (x,y) by using Expression 27 (S6).

Further, the index X can also be approximately calculated using thefollowing Expression 28.

X=−log [SR ₄₁₅(x,y)]+2k log [SR ₄₁₆(x,y)]≅−SR ₄₁₅(x,y)+2kSR₄₁₆(x,y)  (EXPRESSION 28)

A value list indicating the quantitative relationship between the oxygensaturation and the index X experimentally acquired in advance is storedin a non-volatile memory 532 provided to the controller 530. Thecontroller 530 refers to this value list to acquire an oxygen saturationSatO₂ (x, y) which corresponds to a value of the index X calculatedusing Expression 27 or 28. Then, the controller 530 generates image data(oxygen saturation distribution image data) of which pixel value of eachpixel (x, y) is a value obtained by multiplying the acquired oxygensaturation SatO₂ (x, y) by a predetermined value (S7).

Also, the controller 530 generates normal observation image data fromthe R digital image data R₄₁₈ (x, y), G digital image data G₄₁₈ (x, y)and B digital image data B₄₁₈ (x, y) acquired using the illuminationlight IL (white light) that transmitted through the optical filter(ultraviolet cut filter) 418. FIG. 7 shows display examples of imagedata generated by the controller 530. FIG. 7 (a) is an exemplarydisplayed image of the normal observation image data, and FIG. 7 (b) isan exemplary display image of the oxygen saturation distribution imagedata.

Further, the controller 530 generates screen image data for arrangingand displaying the normal observation image and the oxygen saturationdistribution image on a single screen from the generated oxygensaturation distribution image data and normal observation image data,and stores the screen data in the video memory 540. It is noted that thecontroller 530 can generate a variety of screen images such as a screenimage that only displays the oxygen saturation distribution image, ascreen image that only displays the normal observation image, or ascreen image on which associated information such as patient's IDinformation or observation condition is superimposed on the oxygensaturation distribution image and/or the normal observation image inaccordance with the user's operations.

Next, a method for determining the correction coefficient k in thecalibration mode will be described. In the present embodiment, atheoretically calculated index X and a measured index X are compared,and the correction coefficient k is determined such that the measuredindex X becomes closest to the theoretically calculated index X.

FIG. 6 shows exemplary calibration curves used to determine thecorrection coefficient k in the embodiment of the present invention.FIG. 6 (a) is an example of a common calibration curve of which thehorizontal axis is the theoretical index X and the vertical axis is themeasured index X acquired by the above explained analyzing process. Thefilled circles are plots of the measured values, and the broken line Mais a straight line fitted to the measured value by a least-squaremethod. Further, the solid line shows a reference line Ref representingplots in case measured values equivalent to the theoretical values areobtained.

The measured index X is acquired by the analyzing process using a sampleof a biological tissue of which the oxygen saturation is known (e.g.,blood). Further, the theoretical index X defined by Expression 26 iscalculated using transmission spectra of the optical filters 415 and 416to be actually used and a reflection spectrum (or absorption spectrum)of blood. Specifically, the theoretical index X is calculated usingExpression 26 by using a value obtained by multiplying the transmissionspectrum of the optical filter 415 (optical filter 416) by thereflection spectrum of blood and integrating the product as theabsorbance A₄₁₅ (absorbance A₄₁₆).

A discrepancy between the Reference line Ref and the measured value Mais expressed as a gradient of the calibration curve. A phenomenon ofwhich sufficient sensitivity cannot be obtained, that is, a phenomenonof which the gradient is small, is due to an inappropriate quantitativerelationship between the absorbance A₄₁₅ (x, y) and the absorbance A₄₁₆(x, y) in Expression 26, caused by the use of the dimmer filter 419. Byselecting an appropriate value as the correction coefficient k, an errorcaused by the dimmer filter 419 can be corrected, and thus a state inwhich an error between the measured index X and the theoretical index Xis minimized and the measured index X has the highest correlationalrelationship with the theoretical index X can be achieved.

FIG. 6 (b) is a variation of the calibration curve. In the calibrationcurve shown in FIG. 6 (b), the horizontal axis is the oxygen saturationof a sample, and the vertical axis is the index X. The filled circlesare plots of the measured values, and the broken line Ma is a straightline fitted to the measured value by a least-square method. Further, thesolid line Mb shows the theoretically calculated values. It is notedthat the oxygen saturations of the sample are correctly measured valuesacquired from an ideal spectrometry. Being a curve obtained by changingthe horizontal scale of the calibration curve shown in FIG. 6 (a), thiscalibration curve is substantially equivalent to the curve of FIG. 6(a), but there is an advantage that a correct relationship with theoxygen saturation can be easily read.

It is noted that, although the above-explained method for determiningthe correction coefficient k using the calibration curve is a method inwhich analysis results of a plurality of samples having different oxygensaturations are used, the correction coefficient k can also bedetermined using an analysis result from only one sample.

Also, focusing on the absorption wavelength ranges R1, R2 and R3 ofhemoglobin (i.e., the transmission wavelength of the optical filter415), the absorbances A_(R1) (x, y), A_(R2) (x, y) and A_(R3) (x, y)change in accordance with the change in the oxygen saturation, but a sumY of these absorbances (shown in Expression 29) is substantiallyconstant. Furthermore, since the sum Y of the absorbances is inproportion to a total amount of hemoglobin (a sum of oxyhemoglobin HbO₂and deoxyhemoglobin Hb) in a biological tissue, it is reasonable to usethe sum Y as an index for the total amount of hemoglobin.

Y(x,y)=A _(R1)(x,y)+A _(R2)(x,y)+A _(R3)(x,y)=A ₄₁₅  (EXPRESSION 29)

It is known that, in a tissue of a malignant tumor, the total amount ofhemoglobin is greater than that of a healthy tissue due to angiogenesisand the oxygen saturation is lower than that of a healthy tissue due tonotable oxygen metabolism. Therefore, the controller 530 can extractpixels of which the index Y, calculated using Expression 29 andindicating the total amount of hemoglobin, is greater than apredetermined reference value (first reference value) and the index X,calculated using Expression 25 and indicating the oxygen saturation, issmaller than a predetermined reference value (second reference value);generate, for example, lesion region highlighting image data in whichhighlighting process is executed to pixels corresponding to theextracted pixels in the normal observation image data; and display thelesion region highlighting image along with the normal observation imageand/or the oxygen saturation distribution image (or alone) on themonitor 300.

Exemplary highlighting process includes a process for increasing pixelvalues of corresponding pixels, a process for changing color phases (forexample, a process for increasing the R component to change to a reddishcolor or a process for rotating the color phase for a predeterminedangle), and a process for making the corresponding pixels blink (orperiodically changing the color phase).

Further, for example, the controller 530 may be configured to calculatean index Z (x, y) indicating a probability of being a malignant tumor onthe basis of a deviation from an average of the index X (x, y) and adeviation from an average of the index Y (x, y), and to generate imagedata with the index Z (x, y) as pixel values (malign probability imagedata) instead of the lesion region highlighting image data.

The above is an explanation of an embodiment of the present inventionand specific examples of the embodiment. However, the present inventionis not limited to the above configuration and various modifications arepossible within the technical ideas of the present invention.

In the above embodiment, the pixel value of the oxygen saturationdistribution image is calculated by acquiring an oxygen saturation valuefrom the value list in accordance with a value of the index X and bymultiplying the oxygen saturation by a predetermined constant, but thepresent invention is not limited to this configuration. Since the indexX is a value that monotonically increases with the oxygen saturation,the index X itself (or the index X multiplied by a predeterminedconstant) may be used as a pixel value of the oxygen saturationdistribution image.

Further, the image pick-up device 141 of the present embodiment isexplained as an image pick-up device for taking color images comprisingprimary color filters R, G, B on its front face, but the image pick-updevice is not limited to this configuration. For example, an imagepick-up device for taking color images comprising complementary colorfilters Y, Cy, Mg, G may be used.

Further, the image pick-up device 141 of the present embodiment isexplained as a pick-up device for taking color images comprising anon-chip color filter 141 a, but the image pick-up device is not limitedto this configuration. For example, an image pick-up device for takingblack-and-white images may be used to configure an image pick-up devicecomprising a so-called frame sequential type color filter. Also, thecolor filter 141 a is not limited to an on-chip configuration but may bepositioned on a light path between the light source 430 and the imagepick-up device 141.

Further, in the above embodiment, the rotating filter 410 is used, butthe present invention is not limited to this configuration. Other typesof wavelength variable filter of which transmission wavelength can beswitched may also be used.

Further, in the above embodiment, a configuration in which the rotatingfilter 410 is provided at the light source side and the illuminationlight IL is filtered, but the present invention is not limited to thisconfiguration. The rotating filter 410 may be provided at the imagepick-up device side (for example, between the objective optical system121 and the image pick-up device 141) and configured to filter a returnlight from an object.

Further, in the above embodiment, a configuration in which the rotatingfilter 410 is rotated at constant rotation speed while taking images atpredetermined time intervals in the spectral analysis mode is adopted,but the present invention is not limited to this configuration. Forexample, a device may be configured such that the rotating position ofthe rotating filter 410 changes step by step at predetermined timeintervals and images are taken while the rotation of the rotating filteris stopped.

Further, the above embodiment is an example in which the presentinvention is applied to an electronic endoscope device being a form of adigital camera, but the present invention can also be applied to systemsthat use other types of digital camera (e.g., digital single lens reflexcamera or digital video camera). For example, if the present inventionis applied to a digital still camera, observation of surface tissue orobservation of brain tissue during craniotomy (e.g., a quick inspectionof cerebral blood flow) can be performed.

DESCRIPTION OF SYMBOLS

-   1 spectral endoscope device-   100 electronic endoscope-   110 insertion tube-   111 insertion tube tip portion-   121 objective optical system-   131 light guide-   131 a tip portion-   131 b end portion-   132 lens-   141 image pick-up device-   141 a color filter-   142 cable-   200 processor for electronic endoscope-   300 monitor-   400 light source unit-   410 rotating filter-   420 filter control unit-   430 light source-   440 collimator lens-   450 condenser lens-   500 image processor unit-   510 A/D conversion circuit-   520 temporary memory-   530 controller-   540 video memory-   550 signal processing circuit

1. A method for causing a device to generate a distribution image showing a molar concentration ratio between a first biological substance and a second biological substance included in a biological tissue of which an absorption spectrum within a predetermined wavelength range has a first isosbestic point, a second isosbestic point, a third isosbestic point and a fourth isosbestic point in ascending order of wavelength, the method comprising: a step of acquiring first imaging data G₁ by taking an image of the biological tissue using light extracted from white light using a first optical filter configured to collectively selectively extract light in a first wavelength range demarcated by the first isosbestic point and the second isosbestic point, light in a second wavelength range demarcated by the second isosbestic point and the third isosbestic point, and light in a third wavelength range demarcated by the third isosbestic point and the fourth isosbestic point; a step of acquiring second imaging data G₂ by taking an image of the biological tissue using light extracted from the white light using a second optical filter configured to selectively extract light in the second wavelength range; and a step of generating the distribution image on the basis of the first imaging data G₁ and the second imaging data G₂.
 2. The method according to claim 1, wherein the step of generating the distribution image on the basis of the first imaging data G₁ and the second imaging data G₂ further comprises: a step of acquiring an absorbance A₁ of the biological tissue in a transmission wavelength range of the first optical filter on the basis of the first imaging data G₁; a step of acquiring an absorbance A₂ of the biological tissue in a transmission wavelength range of the second optical filter on the basis of the second imaging data G₂; and a step of generating the distribution image on the basis of the absorbance A₁ and the absorbance A₂.
 3. The method according to claim 2, wherein: the step of acquiring the absorbance A₁ includes a step of calculating the absorbance A₁ using Expression 1 or Expression 2; and A ₁=−log G ₁  (EXPRESSION 1) A ₁ =−G ₁  (EXPRESSION 2) the step of acquiring the absorbance A₂ includes a step of calculating the absorbance A₂ using Expression 3 or Expression 4, A ₂=−log G ₂  (EXPRESSION 3) A ₂ =−G ₂  (EXPRESSION 4)
 4. The method according to claim 2, wherein the step of generating the distribution image on the basis of the absorbance A₁ and the absorbance A₂ includes: a step of calculating an index X using Expression 5; and X=A ₁−2kA ₂  (EXPRESSION 5) (where k is a constant) a step of generating the distribution image on the basis of the index X.
 5. The method according to claim 4, wherein the constant k is
 1. 6. The method according to claim 3, further comprising a step of acquiring third imaging data R₃ by taking an image of the biological tissue using light extracted from the white light using a third optical filter configured to selectively extract light in a fourth wavelength range in which an absorbance of the biological tissue is sufficiently low compared to an absorbance in the predetermined wavelength range, wherein the step of acquiring the absorbance A₁ includes: a step of calculating a first standardized reflectivity SR₁ by dividing the first imaging data G₁ by the third imaging data R₃; and a step of calculating the absorbance A₁ using Expression 6 or Expression 7, and A ₁=−log SR ₁  (EXPRESSION 6) A ₁ =−SR ₁  (EXPRESSION 7) wherein the step of acquiring the absorbance A₂ includes: a step of calculating a second standardized reflectivity SR₂ by dividing the second imaging data G₂ by the third imaging data R₃; and a step of calculating the absorbance A₂ using Expression 8 or Expression
 9. A ₂=−log SR ₂  (EXPRESSION 8) A ₂ =−SR ₂  (EXPRESSION 9)
 7. The method according to claim 6, further comprising: a step of acquiring a first baseline image data BL₁ by taking an image of a colorless color reference board using light extracted from the white light using the first optical filter; and a step of acquiring a second baseline image data BL₂ by taking an image of the reference board using light extracted from the white light using the second optical filter, wherein the step of calculating the first standardized reflectivity SR₁ includes a step of dividing the first imaging data G₁ by the first baseline image data BL₁, and wherein the step of calculating the second standardized reflectivity SR₂ includes a step of dividing the second imaging data G₂ by the second baseline image data BL₂.
 8. The method according to claim 6, wherein the fourth wavelength range is 650 nm band, and wherein the third imaging data R₃ is imaging data taken by a light-receiving element, to which an R filter is provided, included in an image pick-up device provided with an RGB color filter.
 9. The method according to claim 4, wherein the constant k is determined such that the index X, acquired on the basis of the first imaging data G₁ and the second imaging data G₂ acquired by taking images of a biological tissue of which the molar concentration ratio is known, becomes closest to a theoretical index X.
 10. The method according to claim 9, wherein the measured index X for each of a plurality of biological tissues, each having a known molar concentration ratio that is different from each other, is acquired and the constant k is determined such that a calibration curve showing a relationship between the known molar concentration ratio and the measured index X becomes closest to a reference line showing a relationship between the known molar concentration ratio and the theoretical index X.
 11. The method according to claim 9, wherein the light extracted from the white light using the first optical filter in the step of acquiring the first imaging data G₁ is dimmed such that an exposure when acquiring the first imaging data G₁ and an exposure when acquiring the second imaging data G₂ become equivalent.
 12. The method according to claim 1, wherein the two types of biological substances are oxyhemoglobin and deoxyhemoglobin, and wherein the molar concentration ratio of the first biological substance and the second biological substance included in the biological tissue is oxygen saturation.
 13. The method according to claim 1, wherein the predetermined wavelength range is a Q band of hemoglobin, and wherein the first imaging data G₁ and the second imaging data G₂ are imaging data taken by a light-receiving element, to which a G filter is provided, included in an image pick-up device provided with an RGB color filter.
 14. A device for generating a distribution image showing a molar concentration ratio between a first biological substance and a second biological substance included in a biological tissue of which an absorption spectrum within a predetermined wavelength range has a first isosbestic point, a second isosbestic point, a third isosbestic point and a fourth isosbestic point in ascending order of wavelength, comprising: a light source which emits white light; a first optical filter configured to collectively selectively extract light in a first wavelength range demarcated by the first isosbestic point and the second isosbestic point, light in a second wavelength range demarcated by the second isosbestic point and the third isosbestic point, and light in a third wavelength range demarcated by the third isosbestic point and the fourth isosbestic point from the white light; a second optical filter configured to selectively extract light in the second wavelength range from the white light; a switching means unit configured to switch between the first optical filter and the second optical filter; an image pick-up device configured to take an image of the biological tissue using the light emitted by the light source; and an image processor unit configured to generate the distribution image on the basis of imaging data generated by the image pick-up device.
 15. The device according to claim 14, wherein the image pick-up device is an endoscope device comprising an endoscope provided at a tip portion. 